Peroxisome proliferator-activated receptors (PPARs), which exert multiple key signaling functions in human skin physiology and pathology, exist in various isoforms. These include canonical (cPPARγ1-4) and dominant negative isoforms (dnPPARγ: γORF4 (γ1-3ORF4), truncated PPARG (PPARγtr) and PPARγΔ5. Yet their exact expression patterns in human skin remain unclear. Therefore, we have localized and quantified PPARγ isoforms in skin biopsies from healthy donors by qRT-PCR or in situ hybridization (for cPPARG). Protein expression was assessed using antibodies that detect all PPARγ isoforms, cPPARγ, or PPARγ2/γ2ORF4. Adipocytes express high levels of mRNA coding for all cPPARG isoforms, PPARGΔ5 and PPARGtr, but minimal levels of GORF4. Lower levels of all PPARG isoforms are also detected in the sebaceous gland (SG), dermis, and epidermis, listed in the order of declining expression. cPPARG2/3/G2/3ORF4 are found most prominently in SGs and dermis, while cPPARG1/4/G1ORF4 expression is comparable in epidermis, dermis and SGs. PPARγtr and PPARGΔ5 expression is higher in SGs as compared to dermis and epidermis. In the hair follicle (HF), the highest expressed isoform is PPARGtr followed by cPPARG1/3/4. cPPARγ transcripts are mainly found in adipocytes, SGs, and mesenchymal skin compartments rather than in the epidermis and HF epithelium in situ. This expression pattern is confirmed at protein level with all selected antibodies. Yet, PPARγ2/γ2ORF4 is almost undetectable in the epidermis but prominent in the bulge. Since we show here cPPARγ and dnPPARγ isoforms to be differentially expressed and distributed within in healthy human skin and its appendages, topically or systemically applied pharmacological PPARγ modulators/agonists are likely to exert compartment-specific, receptor isoform-dependent clinical effects.

ESDR223 - Canonical and Dominant Negative Peroxisome Proliferator-Activated Receptor γ Isoforms are Differentially Expressed in Human Skin and Skin Appendages

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.